PKC-delta phosphorylates CARD9

Stable Identifier
R-HSA-5607740
Type
Reaction [transition]
Species
Homo sapiens
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Activation of NF-kB signaling is a critical event downstream of CLEC7A (Dectin-1), CLEC6A (Dectin-2) (Bi et al. 2010) and CLEC4E (Mincle) (Yamasaki et al. 2008), requiring the adapter protein Caspase recruitment domain (CARD)-containing protein 9 (CARD9) in dendritic cells and in macrophages (Gross et al. 2006, Hara et al. 2007). CARD9 is analogous to CARD-containing MAGUK protein 1 (CARMA1), which mediates T-cell receptor (TCR) activation of NF-kB in lymphocytes. CARD9 is downstream of SYK and becomes phosphorylated by PRKCD (Protein kinase C-delta) phosphorylates CARD9 on Thr-231 (T231), which is required for the signal-induced association of CARD9 with B-cell lymphoma 10 (BCL10) and Mucosa-associated lymphoid tissue 1 (MALT1) and the subsequent recruitment of MAP3K transforming growth factor beta activated kinase 1 (TAK1), leading to activation of the NF-kB pathway (Strasser et al. 2012). A homozygous loss-of-function mutation in human CARD9 results in a premature termination codon (Gln295*). Patients with this mutation are highly susceptible to fungal infections (Glocker et al. 2009).

Literature References
PubMed ID Title Journal Year
22265677 Syk kinase-coupled C-type lectin receptors engage protein kinase C-? to elicit Card9 adaptor-mediated innate immunity

Strasser, D, Neumann, K, Bergmann, H, Marakalala, MJ, Guler, R, Rojowska, A, Hopfner, KP, Brombacher, F, Urlaub, H, Baier, G, Brown, GD, Leitges, M, Ruland, J

Immunity 2012
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Catalyst Activity
Title
calcium-independent protein kinase C activity of DAGs:active p-T507,S645,S664-PRKCD [plasma membrane]
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Activity
Orthologous Events
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